Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells

Journal Article · Tue Dec 15 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.004· OSTI ID:21344808

Ding, M ^[1]; Kisin, E R; Zhao, J; Bowman, L; Lu, Y ^[1]; Jiang, B ^[2]; Leonard, S; Vallyathan, V; Castranova, V ^[1]; Murray, A R ^[1]; Fadeel, B ^[3]

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1. Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States)
2. Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States)
3. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden)

Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC) (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially carcinogenic to humans. However, no comparison of the adverse effects of nano-sized WC-Co particles is available to date. In the present study, we compared the ability of nano- and fine-sized WC-Co particles to form free radicals and propensity to activate the transcription factors, AP-1 and NF-kappaB, along with stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a mouse epidermal cell line (JB6 P{sup +}). Our results demonstrated that nano-WC-Co generated a higher level of hydroxyl radicals, induced greater oxidative stress, as evidenced by a decrease of GSH levels, and caused faster JB6 P{sup +} cell growth/proliferation than observed after exposure of cells to fine WC-Co. In addition, nano-WC-Co activated AP-1 and NF-kappaB more efficiently in JB6{sup +/+} cells as compared to fine WC-Co. Experiments using AP-1-luciferase reporter transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine-sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. Finally, co-incubation of the JB6{sup +/+} cells with N-acetyl-cysteine decreased AP-1 activation and phosphorylation of ERKs, p38 kinase, and JNKs, thus suggesting that oxidative stress is involved in WC-Co-induced toxicity and AP-1 activation.

• OSTI ID: 21344808
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.09.004; PII: S0041-008X(09)00385-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENS
CERMETS
COBALT
EPIDERMIS
HYDROXYL RADICALS
LUCIFERASE
NANOSTRUCTURES
PHOSPHORYLATION
STRESSES
TOXICITY
TRANSCRIPTION FACTORS
TRANSGENIC MICE
TUNGSTEN CARBIDES
ANIMAL TISSUES
ANIMALS
BODY
CARBIDES
CARBON COMPOUNDS
CHEMICAL REACTIONS
COMPOSITE MATERIALS
ELEMENTS
ENZYMES
EPITHELIUM
MAMMALS
MATERIALS
METALS
MICE
ORGANIC COMPOUNDS
ORGANS
OXIDASES
OXIDOREDUCTASES
PROTEINS
RADICALS
REFRACTORY METAL COMPOUNDS
RODENTS
SKIN
TRANSGENIC ANIMALS
TRANSITION ELEMENT COMPOUNDS
TRANSITION ELEMENTS
TUNGSTEN COMPOUNDS
VERTEBRATES